Chromosomal organization of the human dihydrofolate reductase genes: dispersion, selective amplification, and a novel form of polymorphism.
Chromosomal organization of the human dihydrofolate reductase genes: dispersion, selective amplification, and a novel form of polymorphism.
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人类二氢叶酸还原酶基因的染色体组织：分散、选择性扩增和新型多态性。
DOI：
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发表时间：
1984
影响因子：
11.1
通讯作者：
A. Nienhuis
中科院分区：
文献类型：
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作者：
N. Anagnou;S. O’Brien;T. Shimada;W. Nash;M. Chen;A. Nienhuis
人二氢叶酸还原酶(DHFR，四氢叶酸脱氢酶；5，6，7，8-四氢叶酸：NADP+氧化还原酶，EC 1.5.1.3)基因家族包括一个功能基因(HDHFR)和至少四个内含子基因。3个无内含子基因(hDHFR-psi2、hDHFR-psi3和hDHFR-psi4)与有内含子的功能基因的DNA序列有差异，可被鉴定为假基因，而一个无内含子基因(hDHFR-psi1)与功能基因的编码序列完全同源。用特定的分子探针对两组人-啮齿动物体细胞杂交的基因组DNA进行分析，可以深入了解这些基因的染色体组织和分配。这五个基因是分散的，因为每个基因都位于不同的染色体上。功能基因hDHFR位于5号染色体，1个假基因(hDHFR-psi 4)位于3号染色体。在对甲氨蝶呤耐药的人细胞系(HeLa)中，功能基因被扩增，而4个无内含子的假基因均未扩增。HDHFR-psi 1在一些个体的DNA中存在，而在另一些个体的DNA中缺失，这与该基因最近的进化起源一致，最初是因为它与功能基因的编码部分的序列相同。这种无内含子假基因的存在或缺失代表了一种以前未报道的DNA多态形式。
The human dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) gene family includes a functional gene (hDHFR) and at least four intronless genes. Three intronless genes (hDHFR-psi 2, hDHFR-psi 3, and hDHFR-psi 4) are identifiable as pseudogenes because of DNA sequence divergence from the functional gene with introns, while one intronless gene (hDHFR-psi 1) is completely homologous to the coding sequences of the functional gene. Analysis of genomic DNA from two panels of somatic human-rodent cell hybrids with specific molecular probes provide insight into the chromosomal organization and assignment of these genes. The five genes are dispersed in that each one is found on a different chromosome. The functional gene hDHFR has been assigned to chromosome 5, and one pseudogene (hDHFR-psi 4), to chromosome 3. In a human cell line (HeLa) that was selected for methotrexate resistance, the functional locus became amplified, while there was no amplification of the four intronless pseudogenes. hDHFR-psi 1 was found to be present in DNA of some individuals and absent from DNA of others, consistent with a recent evolutionary origin of this gene originally suggested by its sequence identity to the coding portions of the functional gene. The presence or absence of this intronless pseudogene represents a previously unreported form of DNA polymorphism.